Preclinical and clinical evidence that Deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography is a reliable tool for the detection of early molecular responses to erlotinib in head and neck cancer.
Clin Cancer Res
; 16(17): 4434-45, 2010 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-20660574
PURPOSE: There is a clinical need to identify predictive markers of the responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography with computed tomography ((18)FDG-PET/CT) could be a tool of choice for monitoring the early effects of this class of agent on tumor activity. EXPERIMENTAL DESIGN: Using models of human head and neck carcinoma (CAL33 and CAL166 cell lines), we first tested in vitro and in vivo whether the in vivo changes in (18)FDG-PET/CT uptake were associated with the molecular and cellular effects of the EGFR-TKI erlotinib. Then, the pathologic and morphologic changes and the (18)FDG-PET/CT uptake before and after erlotinib exposure in patients were analyzed. RESULTS: Erlotinib strongly inhibited extracellular signal-regulated kinase-1/2 (ERK-1/2) phosphorylation both in the preclinical models and in patients. Western blotting, immunofluorescence, and immunohistochemistry showed that erlotinib did not modify Glut-1 expression at the protein level either in cell line models or in tumor tissue from mouse xenografts or in patients. Phospho-ERK-1/2 inhibition was associated with a reduction in (18)FDG uptake in animal and human tumors. The biological volume was more accurate than the standardized uptake value for the evaluation of the molecular responses. CONCLUSION: These results show that the (18)FDG-PET/CT response is a reliable surrogate marker of the effects of erlotinib in head and neck carcinoma.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Quinazolinas
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Tomografía Computarizada por Rayos X
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Tomografía de Emisión de Positrones
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Neoplasias de Cabeza y Cuello
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia